eChapters

Introduction 
Antimicrobial resistance (AMR) is one of the most significant global health challenges of the 21st century. Defined as the ability of microorganisms— including bacteria, viruses, fungi, and parasites—to resist the effects of antimicrobial drugs, AMR undermines the progress of modern medicine. Antimicrobials—including antibiotics, antivirals, antifungals, and antiparasitics—are the cornerstone of modern medicine. Their discovery transformed the treatment of infectious diseases and enabled surgical advances, chemotherapy, and organ transplantation. However, Alexander Fleming, the discoverer of penicillin, warned that misuse could render these drugs ineffective. Antibiotics, since their discovery in the 20th century, revolutionized healthcare, saving millions of lives and enabling complex medical procedures. Yet, the misuse and overuse of antimicrobials in human health, veterinary practices, and agriculture have rapidly accelerated the emergence of resistant organisms. Today, this warning has materialized as a global crisis. Antimicrobial resistance (AMR) is now considered one of the top ten public health threats by the World Health Organization (WHO). It is not only a biomedical issue but also a socio-economic and developmental challenge. This chapter aims to provide an in-depth overview of AMR, focusing on definitions, history, mechanisms, causes, global status, impacts, and the urgency of mitigation efforts. It also explores national and global responses and future directions to curb the spread of AMR. AMR is estimated to cause 700,000 deaths annually worldwide, with projections of 10 million deaths annually by 2050 if urgent interventions are not implemented. In addition to health impacts, AMR poses grave threats to food security, sustainable agriculture, economic stability, and global development. This chapter provides a comprehensive overview of AMR, including definitions and conceptual frameworks, historical background, mechanisms of

Introduction
The advent of antibiotics, beginning with penicillin in 1941, transformed medicine by rendering bacterial infections treatable [1]. However, antimicrobial resistance (AMR) has emerged as a profound threat, enabling bacteria to survive in the presence of drugs designed to inhibit or kill them and these are rooted in ancient microbial ecosystems evidenced by resistome genes in 30,000-year-old permafrost [2]. AMR has been exacerbated by human practices: approximately 50% of antibiotic prescriptions are inappropriate, 70% of global antibiotics fuel agriculture, and environmental pollution creates resistance hotspots [1]. By 2025, AMR directly causes 1.3 million deaths annually, with economic losses projected at $100 trillion by 2050 [1]. Priority pathogens, including carbapenem-resistant Enterobacteriaceae (CRE), methicillin-resistant Staphylococcus aureus (MRSA), and colistin-resistant strains via mcr-1, challenge last-resort therapies, particularly in low-resource settings [3]. This chapter delivers a technically extraordinary exploration of AMR, structured into genetic, biochemical, and evolutionary mechanisms, each elaborated with molecular precision and step-by-step clarity for learners. Genetic alterations provide the DNA-level foundation, biochemical pathways execute molecular defenses, and evolutionary forces drive adaptation and dissemination. It ensures scientific rigor and broad appeal for students, researchers, clinicians, and policymakers.
Historical Context and Global Burden
AMR emerged shortly after antibiotics’ introduction, with penicillin-resistant S. aureus identified by 1942 due to ß-lactamase production [1]. The 1960s

Introduction 
The discovery of antibiotics—one of the greatest medical breakthroughs of the 20th century—began when Sir Alexander Fleming noticed that the fungus Penicillium notatum inhibited the growth of Staphylococcus spp. This finding sparked a search for similar properties in other fungi and bacteria. From 1940 to 1960, known as the ‘Golden Era of Antibiotic Discovery’, most modern antibiotics such as streptomycin, tetracycline, rifampicin, and nalidixic acid were identified through natural product screening (Clardy et al., 2006; Lewis, 2013). However, the declaration that “it is time to close the book on infectious diseases and declare the war against pestilence won” proved to be premature (Davies & Davies, 2010). It was not a final victory but a fragile truce. In the ongoing war between humans and microbes—nature’s own creations—our successes are brief, and the microbial battleground keeps shifting. Bacteria’s genetic adaptability, coupled with human complacency, led to antimicrobial resistance (AMR), where microbes gradually evolved resistance to almost all known antibiotics (Ventola, 2015). Resistance appeared soon after antibiotics entered clinical use, but the emergence of methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Mycobacterium tuberculosis, and extended-spectrum ß-lactamase (ESBL)-producing bacteria marked major setbacks (Prestinaci et al., 2015; WHO, 2023). AMR gained global attention with the rise of pan-drug-resistant strains—resistant to all antibiotic classes—seen in Klebsiella (India), Acinetobacter, and Pseudomonas (China, Italy, Greece), and extensively drug-resistant tuberculosis (XDR-TB). The infamous case of

Introduction
Antimicrobial resistance (AMR) is one of the top global public health threats. It is estimated that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths (Murray et al., 2019).Despite its magnitude, public awareness of AMR remains low. Unlike tobacco smoke, antibiotics are potentially life-saving medications, but it is just as vital to understand the risks of overuse and their impact on future effectiveness in society as a whole (Langfordet al., 2019). Effective risk communication is essential to addressing AMR because it not only informs professional and community stakeholders but also nurturesbehaviour change across sectors. Within a One Health framework, risk communication connects human medicine, veterinary practice, agriculture, and environmental management, ensuring coordinated responses to reduce misuse and overuse of antimicrobials. This article explores the role of risk communication in combating AMR, highlighting global lessons, challenges, and strategies to strengthen communication systems for sustainable containment.
The Growing Threat of AMR
AMR occurs when microorganisms such as bacteria, viruses, fungi, and parasites evolve mechanisms to resist drugs that once effectively treated them. Misuse and overuse of antimicrobials in human health, livestock, aquaculture, and crop production accelerate resistance. According to WHO, AMR is projected to cause 10 million deaths annually by 2050 if left unaddressed (O’Neill, 2016). In countries like India, with high infectious disease burdens and large-scale antimicrobial consumption, the risks are particularly acute. Communicating these risks clearly and effectively is critical for influencing prescribing practices, agricultural use, and community awareness.Persistent misconceptions include beliefs that antibiotics are effective against viral illnesses and the mistaken notion that it is the human body, rather than bacteria, that develops resistance (Muflihet al., 2021). These knowledge gaps are often linked to insufficient or ineffective health communication (Krockowet al., 2023), sparse media coverage compared to threats like sepsis (Fitzpatrick et al., 2019).
Challenges in AMR Risk Communication
1. Low Public Awareness: Despite the global severity ofAMR, public awareness remains critically low. Surveys have found that a mere fraction of the population grasp its implications, with some reporting only ~8–11% demonstrating adequate understanding and many feeling powerless to contribute (Goshaet al., 2024).
2. Ineffective understanding of Terminology: It is recognized that AMR has a ‘language problem’ and the way in which healthcare professionals communicate about AMR may not always resonate with patients (Langford et al., 2019). Technical labels like “AMR” or “antimicrobial resistance” fall short in public communication. Experiments reveal that phrases such as “Antibiotic Resistance” or “Antibiotic Crisis” are more memorable and better at promoting critical behaviors—like completing prescribed antibiotic courses—than more formal terminology.
3. Misconceptions about Antibiotics: Widespread misunderstandings persist regarding antibiotics’ purpose and effect. Many incorrectly believe antibiotics treat viruses—common colds, flu, or even are effective painkillers (Gunasekara et al., 2022).Some think AMR occurs because the body becomes resistant, rather than bacteria evolving resistance(Muflihet al., 2021).
4. Complexity of the Issue: AMR is inherently multifaceted—spanning interactions among humans, animals, and the environment—which makes it challenging to distill into clear, actionable messages. Understanding Risk

Introduction
Antimicrobial resistance (AMR) represents one of the most significant public health challenges of modern times. The discovery of antibiotics in the early 20th century revolutionized medicine, transforming once-fatal infections into manageable conditions and enabling life-saving procedures such as organ transplantation, chemotherapy, and joint replacement surgery. However, the overuse and misuse of antibiotics in human medicine, veterinary practice, and agriculture have accelerated the development of resistant microorganisms. Today, infections caused by resistant pathogens claim millions of lives worldwide each year, with the World Health Organization warning of a postantibiotic era in which minor injuries or routine surgeries could again become life-threatening. Although AMR is often framed within the context of hospital-acquired infections and clinical treatment failure, its implications extend much further. In particular, AMR has significant consequences for physical and health fitness. For athletes, soldiers, patients in rehabilitation, and physically active individuals, resistant infections can disrupt performance, delay recovery, and compromise long-term health. The increasing prevalence of resistant organisms in community environments—including gyms, swimming pools, and sports facilities—further raises concern. This chapter situates AMR at the intersection of clinical medicine, sports science, and community health. It explores how resistant pathogens affect physically active populations, complicate rehabilitation processes, and influence outcomes in both competitive and recreational Fitnes. It also highlights the global and national responses to AMR, preventive strategies relevant to Fitnes and rehabilitation, and the role of healthcare professionals

Introduction
India has been making steady progress in the livestock sector with significant rise of meat, egg and milk production and a sustained annual growth rate of more than 5%. This growth trajectory is anticipated to accelerate further due to rising middle-class incomes combined with high income elasticity of demand for livestock products. However, despite having huge livestock resource, protein deficiency in rural India remains widespread. Recent data shows that two third of the Indian households are deficient in protein intake1. Looking at the growth potential in the sector, Govt. of India has put special focus on this sector and have undertaken many initiatives to boost animal health productivity and to increase farmer’s income. However, a major limiting factor in profitable livestock production in India is the high prevalence of infectious diseases. These livestock diseases cause great socioeconomic impact and are often exacerbated by inadequate biosecurity measures both in intensive and open production systems. Consequently, the use of antimicrobials for disease treatment has become an essential aspect of livestock management. Antibiotics usage in Animal Healthcare Antibiotics are an essential part of therapeutic management of infectious diseases in both farm and companion animals, ensuring better animal health and life; thereby also assures healthy food from the animal sources. In India a wide range of antibiotics are available in the veterinary practice viz. Penicillin, Semi-synthetic penicillin like Ampicillin, Amoxycillin, Aminoglycosides like Streptomycin, Gentamicin, Neomycin; Tetracycline, Kanamycin, Erythromycin; Fluoroquinolones like Enrofloxacin, Norfloxacin, Ciprofloxacin,

Introduction
Antimicrobial resistance (AMR) poses an escalating threat to global health, eroding the efficacy of antibiotics and complicating the management of bacterial infections. The proliferation of resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae, and multidrug-resistant Mycobacterium tuberculosis, has driven significant increases in morbidity, mortality, and healthcare costs. The ability to detect AMR accurately and promptly is paramount for guiding clinicians in selecting effective therapies, implementing targeted infection control measures, and informing public health strategies to curb the spread of resistant organisms. Conventional methods, rooted in phenotypic assessments, have served as the cornerstone of AMR detection in clinical microbiology laboratories for decades. These techniques evaluate bacterial growth under controlled exposure to antibiotics, offering direct evidence of resistance or susceptibility that molecular approaches, which focus on genetic markers, may miss due to silent mutations, complex regulatory mechanisms, or novel resistance pathways. This chapter provides an exhaustive examination of conventional AMR detection methods, encompassing disk diffusion, broth and agar dilution, gradient diffusion, and automated susceptibility testing systems. These approaches, refined through decades of clinical and research application, remain indispensable for their reliability, cost-effectiveness, and adaptability across diverse settings, from well-resourced tertiary hospitals to laboratories in low-income regions. By exploring their principles, procedures, applications, and limitations, we aim to underscore their enduring significance amidst the rise of rapid molecular diagnostics. The discussion also addresses specialized tests for detecting specific resistance mechanisms, such as beta-lactamase production, inducible clindamycin resistance, and carbapenem’s activity, which are critical for tailoring antimicrobial therapy. Through a critical lens, this chapter evaluates the strengths and challenges of these methods, offering insights into their role in addressing the global AMR crisis, their integration with emerging technologies, and their continued relevance in both routine diagnostics and epidemiological surveillance. The value of conventional methods lies in their ability to translate laboratory findings into actionable clinical decisions. Unlike genotypic methods, which detect resistance genes but may not predict phenotypic behaviour, these techniques assess how bacteria respond to antibiotics under conditions mimicking in vivo environments, aligning closely with therapeutic outcomes. As resistance patterns grow increasingly complex, driven by mechanisms like carbapenem’s and efflux pumps, conventional methods provide a practical foundation for diagnostics, particularly in resource-limited settings where advanced molecular tools are often inaccessible. Their role in global AMR surveillance, such as through the World Health Organization’s Global Antimicrobial Resistance Surveillance System (GLASS), further underscores their importance in tracking resistance trends and informing policy.

Introduction
The emergence and spread of antimicrobial resistance has changed the landscape of infectious disease treatment, creating an urgent need for new diagnostic and therapeutic approaches4’7. Traditional phenotypic antimicrobial susceptibility testing, while remaining the gold standard, requires 24-72 hours for results and provides limited insights into resistance mechanisms. Limited turnaround time is often a constraint that requires empirical use of antibiotics, potentially driving the propagation of other resistance emergence as well as suboptimal patient outcomes. Thanks to mass spectrometry, clinical microbiology has greatly benefitted through the rapid detection of pathogens. However, the application is far broader than species identification. The integration of multiple omics fields like proteomics, metabolomics, genomics, and transcriptomics through mass spectrometry provides unprecedented means to unravel, predict, and combat antimicrobial resistance (AMR) on a molecular level. The use of a multiomics approach is demonstrated to show that AMR is a complex phenotype that arises from the intersection between genetic mutations, variations in gene expression, metabolic differences, and changes in protein structures that all act in unison to affect bacterial survival in the presence of antibiotics. The conversion of raw mass spectrometry outputs into clinical insights amenable to decision-making is dependent upon bioinformatics. Through the use of sophisticated computational methodologies, such as machine learning and network analysis, bioinformatics provides the means to incorporate heterogeneous omics datasets. Through this approach, resistance-related biomarkers can be identified, predictions for therapeutic efficacy can be made, and new targets for intervention can be identified. The intersection between high-resolution mass spectrometry, broad-based omic profiling, and strictbioinformatics provides a powerful platform for addressing the intractable challenge of antimicrobial resistance.

Antimicrobial resistance (AMR) is a mounting global health emergency that threatens the effectiveness of modern medicine and veterinary care. In India, the challenge is compounded by high antibiotic consumption, unregulated access to antimicrobials, and widespread use in agriculture and animal husbandry. The World Health Organization has identified the Eskape pathogens— Enterococcus faecium, Staphylococcus aureus, Klebsiellapneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp, as priority organisms due to their ability to “escape” the effects of antibiotics and cause life-threatening infections. Simultaneously, zoonotic transmission of resistant bacteria from animals to humans is emerging as a critical concern, particularly in regions with close human-animal interfaces like Jammu & Kashmir. The importance of Eskape pathogens to the establishment and promotion of antimicrobial resistance in hospitalized patients was first recognized in a 2008 by Rice. The morbidity and mortality associated with Gram-negative Eskape pathogens is particularly concerning, as new antimicrobial agentsthose with activity against multidrug-resistant and pan-resistant Gram-negative strainshave not emerged as quickly as needed. Consequently, nosocomial infections continue to pose a serious threat to patient health, especially among critically ill inpatients and those undergoing invasive procedures or requiring the placement of medical devices. Eskape pathogens are well known for their intricate resistance mechanisms, often leaving clinicians with limited therapeutic options. Due to their significant role in driving antimicrobial resistance within hospital settings, consistent and systematic monitoring of their resistance profiles is crucial for guiding effective infection control and therapeutic strategies.This also serves as a critical indicator of regional resistance trends among hospitalized populations. In animal sector, the wastewater of livestock slaughterhouses, animal products (raw or processed) have been considered a source of multidrugresistant bacteria with clinical implications as well as their dissemination into the environment and entry into human food chain.Bacteria from the livestock can act as opportunistic pathogens and carry resistance genes that are important for both veterinary and human health. Since many antibiotics are used in both human and animal health fields, the resistant bacteria enter the environmentespecially through wastewater treatment plants affected by slaughterhouse wasteposing risks to public health. Among the various sources, the water used during poultry slaughtering often contains multidrug-resistant bacteria and can expose slaughterhouse workers to infection. To reduce these risks, it’s important to develop strategies that limit bacterial release into the water systems and prevent their spread to people and the environment. The development of AMR has been attributed to several factors comprising of microbial mutations rendering the antibiotics ineffective, human interference such as over use and over-prescription of antimicrobials, agricultural and commercial application of antimicrobials in the animal sector, and human behavioural factors (Vijayalaxmi et al., 2021). An expected annual rise of antimicrobial resistance (AMR) by 5–10 % annually has been predicted by the Indian Council of Medical Research (ICMR) Annual Report 2021 due to wide spread abusive use of broad-spectrum antibiotics (ICMR Annual Report 2021). Twelve families of priority drug-resistant bacteria (critical, high and medium) posing great threat to human health in terms of resistance to selected antimicrobials have been identified in priority pathogen list (PPL) of Global Action Plan, World Health Organisation (WHO) to stimulate the research towards the development of new antimicrobials against a particular drug-resistance (WHO,2017). From the Indian perspective, AMR is a grave concern as the Indian population is the highest consumer of antibiotics in the world (10.7 units per person). The poor public health systems, hospital infections, high rate of infectious diseases, easy availability of inexpensive

Introduction
Infection prevention and control refers to prevention and control of infections and their transmission in healthcare settings. Healthcare Associated Infections (HAI) are one of the most common adverse events in delivery of care and a major public health problem with an impact on morbidity, mortality and quality of life. Up to 7% of patients in developed and 10% in developing countries acquire at least one HAI. These infections also present a significant economic burden for the health system.1It is evident that HAIs result in prolonged hospital stays, long-term disability, increased resistance of microorganisms to antimicrobials, additional cost on health systems, high cost for patients and their family, and preventable deaths.
The core components of IPC2
• IPC programme at the national and health facility level
• National and facility level evidence-based guidelines on IPC
• Education and training
• HAI surveillance
• Multimodal strategies
• Monitoring and audit of IPC practices and feedback
• Workload, staffing and bed occupancy
• Built environment, materials and equipment for IPC
HAI Burden
HAI are one of the most common adverse events in healthcare delivery and a major public health problem with an impact on morbidity, mortality and

Introduction
Antimicrobial resistance (AMR) is regarded as a silent pandemic that is responsible for causing the majorityof deaths every year and has become a major healthcare challenge and a significant public health issue. It has been reported that AMR alone has caused more fatalities than road accidents and cancer. It is among the top ten global health threats and has been recognized as a part of the multisector One Health approach. It has been predicted that by the year 2050, the burden of AMR will decrease the gross domestic product (GDP) by 2 to 3.5%, causing a loss of USD100 trillion to the world, with the annual death rate reaching 10 million. India faces one of the world’s highest antimicrobial resistance (AMR) rates, driven by high antibiotic consumption in humans, widespread non-prescription use, and unregulated application in livestock, aquaculture, and agriculture. Surveillance data show alarming resistance in major pathogens E. coli and Klebsiella,which now exhibit very low susceptibility to key antibiotics such as cefotaxime, ciprofloxacin, and carbapenems. Factors exacerbating the burden include inadequate infection prevention, limited laboratory capacity, poor enforcement of regulations, environmental contamination from pharmaceutical and hospital waste, and low public awareness. The combined impact threatens public health, food safety, and the economy. In general terms, AMR is defined as the ability of the microorganisms to withstand the action of an antimicrobial agent,i.e. Antibacterial agents, antifungal agents, potentially toxic metals, and disinfectants. AMR is known to be a natural process that occurs over time due to genetic changes in the pathogens under selective pressure, where a pathogen undergoes mutations and is often linked to indiscriminate use of antimicrobial agents.
Indefinite and improper use of antimicrobial agentshas been a major factor in the emergence of AMR. AMR affects both animals and humans alike, and resistant pathogens pose a challenge in treating infections. One of the crucial factors responsible for AMR is theenvironment, which is regarded as both a vehicle for spreading AMR microbes as well is a culprit of AMR pollutants, which severely impact the ecosystems. AMR is a multifaceted problem and to control it effectively, meticulous measures have been implemented for monitoring and surveillance of AMR in clinical settings, in both human and veterinary fields. However, the environmental surveillance dealing with the environmental AMR has yet to be established. The implementation of comprehensive monitoring of AMR in environment will vastly improve our understanding of the various dissemination routes and propagation of the resistant microbes in environment and their role in spreading AMR. In this chapter, we will discuss the environmental spread of AMR, drivers of AMR in the environment, factors influencing AMR, challenges faced, measures to tackle AMR, and future trends in curbing the burden of AMR.

Introduction
Aquaculture is one of the sunrise sectors contributing a significant quantity to the global supply of fish for human consumption. Fish is a superior source of highquality animal protein and highly digestible energy. Disease problems in farmed fishes are one of the main barriers, resulting in significant financial losses up to a tune of US$2.48 B, 14.95% of the annual aquaculture production value in Indian aquaculture. In the aquatic environment, bacteria are quite prevalent and the majority of bacterial pathogens are found in the water’s natural flora. They only spread illness when poor husbandry practices, inadequate nutrition, and unfavourable environmental circumstances contribute to fish stress. Pathogenic bacteria, including Aeromonas spp, Escherichia coli, Staphylococcus spp, Salmonella spp., Shigella spp., Yersinia enterocolitica, Clostridium botulinum, Plesiomonas shigelloides, and Listeria monocytogenes, can be either naturally present in fish or introduced to them during handling, processing, and storage. Antimicrobial resistance (AMR) in Indian aquaculture presents a multifaceted and growing challenge at the intersection of public health, environmental sustainability, and food security. As aquaculture expands to meet rising global demands for protein, the sector has increasingly relied on antimicrobials to prevent and treat bacterial infections. However, due to some indiscriminate and unregulated use of these agents as well as the householdsewage, hospital effluents, contamination from agricultural wastes andinadequately treated urban waters that enter the aquaculture through drains and rivers,creates strong selective pressure and accelerate the development and dissemination of resistant pathogens in aquatic environments posing a serious threat not only to farmed fish but also to human health through environmental contamination and the broader food chain. Resistant bacteria and resistance genes can spread through water systems, biofilms, and aquaculture products, creating reservoirs that contribute to the broader One Health AMR crisis. Food borne pathogens (Aeromonas spp., Vibrio spp., and Streptococcus spp.) from aquatic animals were found resistant to antimicrobial agents that are relevant for therapeutic usage in human clinical settings. E. coliwas found to be resistant as a sign of possible human and terrestrial animal effects. Distinguishing resistance that has been selected in different sectors is extremely difficult and caution is needed while trying to attribute the source of antibiotic resistance in bacteria in the aquatic environment. Understanding the drivers, mechanisms, and impacts of AMR in aquaculture is essential for developing effective mitigation strategies and sustainable management practices that safeguard both aquatic and human health.

Introduction
Antibiotic-resistant E. coli develops as a result of the heavy use of antibiotics in the production of food animals, which is then found in the meat from those animals. There have been reports of a number of antimicrobial resistant E. coli infections linked to the ingestion of tainted milk and chevon. As a result, the existence of antibiotic resistant E. coli is a significant and expanding global public health risk. Escherichia coli of animal origin has also been seen to colonise humans, and because it is resistant to many conventional antibiotics, it can cause serious illnesses for which there are few effective treatment choices. Due to its ubiquitous presence in the environment, E. coli has traditionally been recognised as the main vehicle for the transmission of various antibiotic resistance genes and vectors.Extended-spectrum beta-lactamases (ESBLs), which can make the bacteria resistant to some frequently used antimicrobial treatments, are tiny proteins (enzymes) that some strains of E. coli have been shown to manufacture under favourable conditions. A major issue around the world is the emergence of different E. coli strains that produce ESBL in foods that come from animals that are raised for food. The ESBL enzymes TEM, SHV, and CTX-M from Group A have been widely reported to be generated by E. coli and have been shown to hydrolyze ampicillin, carbenicillin, oxacillin, and an extended spectrum of cephalosporins, including ceftazidime and cefotaxime.
Extended beta spectrum lactamase producing E. coli
The occurrence of antimicrobial resistance and the presence of corresponding resistance genes in the environment is an ancient phenomenon. This is largely due to the fact that many of today’s antimicrobial agents are derived from natural precursors produced by soil bacteria such as Streptomyces. These natural compounds likely evolved to mediate microbial competition for

Introduction
Antimicrobial resistance (AMR) is a global concern that poses a significant threat to contemporary healthcare systems, potentially hindering the management and treatment of various diseases. Microorganisms can act as reservoirs for AMR across various ecological niches; thus, a “one health” proposal is essential for coordinating a multisectoral strategy aimed at investigating and tackling this alarming issue. This method seems to be an effective strategy for addressing and alleviating the challenges posed by AMR; however, it demands the collaborative efforts and assets that are consistently and efficiently executed by health practitioners. Horses have been pivotal in human history; they have served in wars, provided transportation, and even aided in mining operations. In contemporary society, horses are significant as sport animals and in therapeutic settings involving animals. Given these close interactions between humans and equines, it becomes essential to effectively identify infectious diseases and antimicrobial resistance (AMR) impacting both species, particularly in instances of highly contagious diseases. Resistant bacteria represent a significant threat to the health of both equines and humans. Horses may obtain resistant bacteria through several avenues, such as interaction with other animals, exposure to contaminated materials, or to antibiotic uses. The responsible utilization of antibiotics and the implementation of antimicrobial stewardship programs are essential in reducing the transmission of antimicrobial resistance (AMR) within equine populations. A variety of zoonotic pathogens that exhibit resistance to antibiotics has been identified in equines. This includes Extended-Spectrum Beta-Lactamases (ESBL) which produces E. coli, Methicillin-Resistant Staphylococcus Aureus (MRSA), and Multidrug-Resistant (MDR) Salmonella. Horses can develop AMR through various channels like:

Introduction
Haemoprotozoan diseases are highly prevalent in tropical and sub-tropical countries owing to the ubiquitous distribution of ticks and blood-sucking flies which are natural vectors for the pathogens. In India, theileriosis, babesiosis and trypanosomosis are major haemoprotozoan diseases and cause substantial economic losses to the livestock industry. Though vaccination of the susceptible stock by attenuated schizont vaccine is available for the control of tropical theileriosis in cattle, chemotherapy is the mainstay for the control of haemoprotozoan diseases. However, the limited available antihaemoprotozoan drugs is being depleted by a combination of two factors viz. emergence of drug resistance and the failure to replace old drugs (de Koning, 2017). Drug resistance against parasites is one of the emerging problems affecting veterinary health sector. Since last few decades, development of drug resistance in haemoprotozoan parasites to several drugs has been reported (Tuvshintulga et al., 2019; Ali et al., 2022). Though, understanding of drug resistance in parasitic protozoa is progressing steadily but possibly not as rapidly as parasites are becoming resistant to drugs. The genetic changes in the target sites, the reduced uptake and increased efflux of drugs, and metabolic regulations are the possible mechanism for the cause of drug resistance (Fairlamb et al., 2016). Anti-protozoan drug resistance has been reported in many economically important protozoa to isometamedium, diminazene aceturate, quinapyramine, suramin, melarsomine dihydrochloride, buparvaquone. The resistance initially evolves at genetic level of parasite with genetic traits that allow them to survive exposure to a drug, which is transferred to the subsequent generation thereby potentially increasing the percentage of resistant parasite that can survive subsequent exposure to the chemical. The emergence of drugresistant parasites has serious implications for treating clinical cases, leading to increased morbidity and mortality among the animals and control of the diseases.

Introduction
Antimicrobial resistance (AMR) is a mounting global crisis that threatens public health, food security, and development. The rapid spread of resistant pathogens has rendered many conventional antibiotics ineffective, leading to longer illnesses, increased mortality, and escalating healthcare costs(1)(2). The World Health Organization characterizes AMR as a top-ten global health threat, driven by overuse, misuse, and inadequate dosing of antibiotics. It already kills 700,000 people a year and is expected to kill 10 million people a year by 2050 if nothing is done about it(3). After penicillin was introduced to the market in 1941, the first signs of resistance appeared in staphylococci, streptococci, and gonococci. By 1942, Staphylococcus aureus, which was penicillin-resistant, emerged(4). Drug resistance must be effectively addressed for a few reasons, including public health, economic considerations, and the long-term viability of medicine. Maintaining the effectiveness of existing treatments for infectious diseases is an important objective(5). NDDS technologies have emerged as powerful tools to enhance the delivery, bioavailability, and targeting of antimicrobial agents, potentially reviving older antibiotics, and maximizing the efficacy of novel compounds(6). Parallelly, AI has found impactful applications in biomedical data analysis, drug discovery, and the rational design of therapies by processing complex datasets, predicting resistance patterns, and guiding the creation of new molecules. The integration of AI with NDDS marks a paradigm shift to optimizes delivery systems, guides individualized treatment plans, and advances the field towards precision medicine for infectious diseases (7). This chapter surveys the convergence of these technologies, exploring how AIenhanced NDDS platforms are reshaping the response to AMR. Additionally, it examines diverse AI models and algorithms employed in the prediction, optimisation, and management of drug resistance, enhanced by real-time case studies for thorough comprehension(fig1.).

Introduction
 Antibiotic therapy is one of the mainapproaches of modern medicine used tofight bacterial diseases worldwide.Antibiotics comprise of any natural, synthetic, or semi-synthetic substances which interfereswith the growth and development of microbes or have killing effect onmicrobes, specifically bacteria. The availability of these antibiotics for treating various bacterial infectious diseases significantly improved the quality of life of humans as well as animals.The period from1930s to 1960s is considered as the ‘golden era’ of antibiotics during whichmost of the antibiotics available today werediscovered. Antibiotics, once known as the magic bullets of modern-day medicine, are now an “endangered species” facing the danger of extinction due to the worldwide emergence of antibiotic resistance (ABR)/antimicrobial resistance (AMR) among microbes. In general, AMR is the capacity of a microbes (bacteria, fungi, and viruses) to resist the growthinhibitory or killing activity of an antimicrobial beyond its normal susceptibility by altering their physiologyor genetic makeup. AMR has emerged as one of the most critical and complicated global public health threat due to its multi-faceted nature.World Health Organization (WHO) has declared AMR as one of the top 10 global public health threats. The emergence of AMR is closely related to the extensive use and misuse of existingantibiotics in the human and animal fields without properguidelines as well as failure to developor discover new antibiotics. AMR leads to a significant health burden worldwide as it is estimated that bacterial AMR alone attributesto 1.14 million deaths globally in the year 2021 and if left unchecked, it may contribute to 10 million deaths annually by 2050.This prediction was recently updated with the data from 2019 and reported that the deaths of 4.95 million people were related to drug-resistant bacterial infections and 1.27 million deaths were directly attributable to AMR.In addition to the health burden, AMR also increases the healthcare costs and imposes significant indirect economic burdens.Increasing reports of treatment failures in patients with infections caused by multi-, extensive-, and pan-drugresistant bacteriahave been documented in literature from different part of the world. Antibiotics once normally used to treat bacterial infections are no longer effective, and it becomes vital to use “reserve” or “last resort” antimicrobials that are often more expensive. Furthermore, WHO has also emphasized that AMR not only makes infections harder to treat but also jeopardizes ancillary medical procedures such as surgeries and cancer treatments. Food may act as a carrier for the transfer of antimicrobialresistant bacteria (AMRB) and antimicrobial resistance genes (ARGs) to humans.Many scientific reports establish a link between the extensive use of antibiotics duringagricultural production and the increase in AMRamong human pathogens, in which food is one of thepossible transmission routes. Antibiotics are regularly added to feed as additives in intensive animal production systems at sub-therapeutic doses to stimulate growth, improve feed efficiency and avoid infections. The extensive use of antibiotics in human treatment, animal therapy and agricultural use as growth promoters are further causes of bacterial resistance to antibiotics. In recent years, the prevalence of AMR among microorganisms isolated from animal source foods (milk, meat, eggs etc) has increased. The increasing demand for quality animal protein has driven intensive farming, leading to increased antimicrobial usage. In the year 2020, global antimicrobial consumption in food-producing animals was estimated around 99,502 tonnes.Antibiotics are commonly used prophylactically infoodproducing animals and it is projected that by 2030 such usewill increase by approximately 67% globally.Despite efforts to reduce antibiotic use, many countries still rely heavily on antimicrobials for growth promotion and disease prevention. The Food and Drug Administration (FDA) has emphasized the need for better monitoring of antimicrobial use in animals. The emergence and spread of AMR in the food chain is considered as a multisectoral issue, because (i) antibiotics are widely used in livestock production systems (cattle, poultry etc), (ii) AMRB and ARGs can easily spread at each stage of the food production chain, and (iii) these AMRB can cause infections in humans.Thus, the emergence of AMR along the food chain is a major

Introduction
The discovery of antibiotics in the early 20th century revolutionized medicine, agriculture, and public health. These compounds, capable of inhibiting or destroying pathogenic bacteria, not only saved millions of human lives but also transformed animal production systems by reducing morbidity and mortality, improving growth rates, and ensuring food security (Phillips et al., 2004). The application of antibiotics in food animals,whether for therapeutic, prophylactic, or growth-promoting purposes,has been instrumental in increasing global meat, milk, egg, and fish production, thus addressing the nutritional needs of a growing population (Darwish et al., 2013; Chen et al., 2019). However, the indiscriminate and excessive use of antibiotics in animal agriculture has created unintended consequences, most notably the presence of antibiotic residues in foods of animal origin and the global acceleration of antimicrobial resistance (AMR) (Bacanli & Basaran, 2019; Shahid et al., 2021). Antibiotic residues in food is the trace amounts of active compounds or its metabolites that remain in edible animal tissues, milk, eggs, and aquaculture products causes significant concerns for both consumer safety and public health. Even when below the maximum residue limits (MRLs) established by regulatory authorities, prolonged exposure may lead to allergic reactions, disruption of the gut microbiome, reproductive and developmental toxicity, mutagenicity, nephropathy, and in certain cases carcinogenicity (Ngangom et al., 2019; WHO, 2020). Furthermore, residues contribute to the selection pressure that drives the emergence and dissemination of resistant bacterial strains in humans, animals, and the environment (FAO, 2019; O’Neill, 2016). The One Health framework highlights these interconnected pathways, recognizing food as a critical link between veterinary antibiotic use and human AMR burden (Robinson et al., 2016). Globally, approximately 73% of antibiotics are consumed in food animal production, with projections estimating a further 11–67% increase by 2030,largely by intensification of livestock and aquaculture in developing economies (Van Boeckel et al., 2015; Tiseo et al., 2020). While industrialized nations have implemented bans on antibiotic growth promoters and introduced robust surveillance programs, most low- and-middle-income countries still facing challenges (Antibiotics, 2021; WHO, 2019). Consequently, foods containing antibiotic residues frequently enter local and international markets, undermining food safety standards and exacerbating AMR risks (Darwish et al., 2013; Antibiotics, 2021). Antimicrobial resistance (AMR) has emerged as a major global public health crisis, directly causing an estimated 1.27 million deaths and contributing to nearly 5 million deaths worldwide in 2019. Recognizing its severity, the World Health Organization (WHO) has identified AMR as one of the top ten threats to global health(Murray et al., 2022). By 2050, global economic losses linked to AMR are projected to reach USD 100–210 trillion, with Asia bearing a disproportionate mortality burden (O’Neill, 2016). Countries like India, with large livestock populations, rapidly growing aquaculture industries, and high human antibiotic consumption, represent critical hotspots where food, health, and environmental risks intersect (Chauhan et al., 2018; ICMR, 2020). Given these alarming trends, understanding the occurrence, detection, and consequences of antibiotic residues in foods of animal origin is paramount. This chapter explores the co-relationship between origin of antibiotic residues and AMR, regulatory measures aimed to safeguard food safety and strategies for prevention and control, framed within the One Health approach.

Introduction
Antimicrobial resistance (AMR) has become a major worldwide health issue, requiring the search for natural, safe, and efficient substitutes for synthetic antibiotics. The ancient medical system known as Ayurveda lists a variety of polyherbal compositions having jwaraghna (antipyretic) and krimighna (antimicrobial) qualities. A traditional decoction preparation that is frequently prescribed for microbial infestations (krimi), wound infections, fevers, and skin conditions called Nimbadi Kwatha.Strong herbs that have been separately shown to have antibacterial and immunomodulatory properties, including Nimba (Azadirachta indica), Guduchi (Tinospora cordifolia), Triphala (Haritaki, Bibhitaki, Amalaki), Vasa (Adhatoda vasica), and Katuki (Picrorhiza kurroa), make up Nimbadi Kwatha. Triphala has antimicrobial and antioxidant qualities, Guduchi boosts host immunity and has antibacterial qualities, and Neem provides broad-spectrum antibacterial, antifungal, and antiviral activity. According to experimental studies, giloy extracts are effective against a variety of pathogens, such as bacteria, viruses, and fungi. It has a distinct antimicrobial activity that involves two mechanisms: it enhances phagocytosis, changes cytokine production, and activates macrophages. In light of antimicrobial resistance (AMR), T. cordifolia is a prospective option for the development of plant-based antimicrobials and integrated therapies. Its use is backed by both modern pharmacological research and ethnomedicinal history for infectious disorders and immune health. Nimbadi Kwatha and its derivatives, including Nimbadi Ubatan and soap formulations, have been shown to have antibacterial properties by modern pharmacological research, which also showed a notable inhibition of bacterial and fungal growth in vitro. These results demonstrate the value of Ayurveda in treating infectious diseases and lend credence to its traditional claims. To close the gap between traditional knowledge and contemporary evidence, a thorough analysis of Nimbadi Kwatha’s antibacterial impact is essential. It also identifies the plant’s potential as a natural remedy for drug-resistant infections.

Introduction 
The discovery and introduction of antimicrobial agents to clinical medicine was one of the greatest medical triumphs of the 20th century that revolutionized the treatment of bacterial infections. However, the gradual emergence of populations of antimicrobial resistant pathogenic bacteria, resulting from use, misuse and abuse of antimicrobials has today become a major global health concern. Antibacterial drugs have revolutionized our ability to control bacterial disease, and their clinical availability has led to dramatic decreases in morbidity and mortality. (Walsh and Wright, 2005). As such, these therapeutics underpin modern medicine. Despite the integral role of antibiotics in sustaining our modern lifestyle, they are undervalued in both cost and significance by society. Over the past century, their use has provided strong selective pressure on microorganisms, leading to preferential survival and spread of those harbouring antibiotic resistance mechanisms. Multidrug resistance is now commonplace amongst bacterial pathogens with antibiotic resistance now affecting all antibiotic classes. (Coates et al, 2011). This is particularly worrisome in the case of Gram-negative bacteria (e.g. Pseudomonas aeruginosa and Acinetobacter baumannii) for which treatment options are already limited. The ‘broken’ economics of antibacterial research and development is often quoted as the main reason for the lack of new therapies but the truth is that it is hard to discover new antibacterial drugs, and the science is not sufficiently advanced to allow discovery of efficient and effective drugs. This has led to fears of a ‘post-antibiotic era’ as it has been estimated that 5–20 novel antibacterial drugs need to enter clinical development in order to effectively contend with the current resistance problem. However, given the attrition rate within the existing drug discovery model, at least 200 discovery programmes would be needed in order to achieve this outcome. Hence, new approaches to antibiotic discovery are needed. The antibiotic pipeline The antibiotic pipeline is not what it once was.4 Pharmaceutical companies were once the main provider of novel antibiotic molecules but they largely withdrew in the late 1990s because of the lack of success and low financial returns in bringing new antibacterial drugs to the market.5 The environment of discovering and developing new antibiotics was quite different during the so-called ‘golden era’ of drug discovery. Antibiotics worked remarkably well because resistance was low and physicians had access to a variety of efficacious antibiotics. Antibiotic research and development programmes were inclined to focus on improved pharmacology to achieve less frequent dosing e.g. once a day, rather than innovative new antibiotics. Natural product screening strategies tended to result in rediscovery of compounds rather than finding new ones. There was also no need to consider those natural products with undesirable properties such as toxicity. Today, only a few large companies such as GlaxoSmithKline, Novartis, Merck and Roche are still actively engaged in antibiotic R&D, with many of the original antibiotic provide.The natural world remains the largest source of novel drug scaffolds making this a viable option in the search for new antibiotic compounds. Advances in bacterial culture techniques, molecular biology and metagenomics will make natural product drug discovery easier and more costeffective, obviating these limiting factors. Screening procedures must include whole-bacterial cell assays, addressing the issue of bacterial permeability and efflux early in the discovery process (Shore and Coukell, 2016). Additionally, the generation of training schemes by, and with, pharmaceutical companies that cover all aspects of the pipeline and include natural product drug discovery, are essential and will ensure that expertise is passed on to future researchers. Investment should also be made into the study of previously characterized lead compounds that did not reach the clinic, so called old leads. The reasons that led to these compounds being dropped from further development vary, ranging from financial issues to trial design, dosing problems and toxicity. It may be that there is now sufficiently improved technology and expertise to develop these as safe and efficacious antibacterials. The revival of interest in old leads could also provide an additional source of novel antimicrobials. A freely accessible database of antibiotics that were never developed has recently been launched, Antibiotic with the aim to reduce unnecessary duplication of Pharmaceutical agents such as nanospheres, liposomes, and immunoglobulins for example have been developed which can alter the pharmacodynamics of a compound, act as carriers for sustained or controlled drug release, and for immunization therapy.